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Biomarker for Brain Excitability May Help Track Medication Effect

Science Update

A newly discovered link between order in the activity of neurons in the brain and excitability—how likely it is that individual neurons will “fire”—may provide a means for monitoring treatment of conditions like epilepsy that would be less invasive and thus more versatile than current methods. This new approach, developed by NIMH scientists, has implications beyond conditions like epilepsy; the findings support an emerging picture of how the brain balances flexibility and order during wakefulness and sleep.

The brain is a network of billions of neurons that “excite” each other. These interactions must be balanced across the brain to allow brain networks to function properly without tipping into chaos. NIMH researchers Christian Meisel and Dietmar Plenz led a collaboration of scientists from the USA, Germany, Australia, and Switzerland to investigate how the brain achieves this balance by tracking the level of order in neuronal activity. Previous studies using computers and cell culture had suggested that the degree of order is closely related to the degree of excitability. When excitability is low, network activity is disordered; as excitability grows, a point is reached where order abruptly emerges, reminiscent of a phase transition like that which occurs as water turns to ice.

In this work, the scientists identified a close relation between network order and network excitability in the human brain. They analyzed the level of order in brain activity recorded over many days in patients suffering from epilepsy and showed that measures of spontaneous order track with conventional measures of excitability that use electrical or magnetic stimulation. Importantly, they showed that in patients taken off antiepileptic medication, brain networks were at the threshold between disorder and order: exactly what earlier work predicted would be true for the living brain. In contrast, brain networks became less ordered, when the dosage of antiepileptic medication was increased. (Antiepileptic medication reduces excitability.)

In humans suffering from epilepsy, seizures result from abnormal changes in neuronal excitability; the reduction of excitability with antiepileptic drugs is therefore of prime clinical importance. “By simply monitoring spontaneous brain activity, the amount of order in the brain can be quantified, providing information about the underlying excitability of brain networks,” said NIMH scientist Christian Meisel. Up to now, reliable measures of brain excitability had been difficult to obtain. In the clinical environment, this new approach might be particularly useful because traditional measures of excitability relied on active perturbation of the brain which often cannot be used in epilepsy patients and over longer periods of time.

Taking advantage of the new approach for long-term monitoring, the researchers demonstrated that order and—consequently excitability—in the brain increases during the day and decreases at night. Thus, sleep seems to be important in rebalancing excitability in the brain. Such versatile monitoring of excitability levels in patients could guide more individualized treatment strategies.  

This study is online ahead of print in the Proceedings of the National Academy of Sciences.

Reference

Meisel C, Schulze-Bonhage A, Freestone D, Cook MJ, Achermann P, Plenz D. Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle.  Proc Natl Acad Sci U S A. 2015 Nov 9. pii: 201513716. [Epub ahead of print]